Chronic myelogenous leukemia (CML) is a multipotent stem cell disorder associated in over 90% of cases with the Philadelphia chromosome (Ph1). Alterations of the c-abl oncogene have been previously described in CML: this gene is translocated to the Ph1in cases of CML; and an abnormally large c-abl RNA transcript (8.2 kb vs the normal 7.4 and 6.6 kb), which may be related to the pathogenesis of CML, has been observed in Ph1positive CML cells. This proposal aims to molecularly clone DNA sequences which are present in the 8.2 kb abl CML transcript but not in the normal 7.4 and 6.6 kb abl transcripts. This DNA clone will provide a relatively simple means of quantitating expression of the 8.2 kb abl transcript in various CML cells. The following questions will be specifically addressed using the 8.2 kb abl transcript-specific probe: (1)\How strict is the correlation between the presence of the Ph1and the presence of the abnormal 8.2 kb abl transcript? (2)\Are there subsets of CML cells in which the 8.2 kb abl transcript is preferentially expressed? (3)\Is there a relationship between enhanced expression of this transcript and progression of CML from chronic to blast crisis phase? In addition, if there is found to be a strict correlation between the presence of the Ph1and the presence of the 8.2 kb abl transcript, then attempts will be made to perfect a diagnostic and prognostic test for CML utilizing the 8.2 kb abl transcript-specific DNA probe. This test potentially would be more rapid, simpler, and capable of screening a larger number of samples that the cytogenetic demonstration of the Ph1which currently is the best diagnostic marker for CML. (6)